Skip to main content
Erschienen in: Lasers in Medical Science 1/2018

28.11.2017 | Original Article

Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers

verfasst von: Anelice Calixto Ruh, Lúcio Frigo, Marcos Fernando Xisto Braga Cavalcanti, Paulo Svidnicki, Viviane Nogaroto Vicari, Rodrigo Alvaro Brandão Lopes-Martins, Ernesto Cesar Pinto Leal Junior, Natalia De Isla, Francesca Diomede, Oriana Trubiani, Giovani Marino Favero

Erschienen in: Lasers in Medical Science | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm2, once a day, with intervals of 24 h, totaling 12 applications. The lesion area analysis revealed averaged improvement of the granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis revealed that IL6 values were not significantly different before and after treatment, TNF gene expression was reduced, and VEFG and TGF-β gene expression increased after treatment. After LLLT, wounds presented improvement in gross appearance, with increase in factors VEFG and TGF-β, and reduction of TNF; despite our promising results, they have to be analyzed carefully as this study did not have a control group.
Literatur
1.
Zurück zum Zitat Calil JA, Ferreira LM, Neto MS, Castilho HD, Garcia EB (2001) Clinical application of the VY posterior thigh fasciocutaneous flap. Rev Assoc Méd Bras 47(4):311–319CrossRefPubMed Calil JA, Ferreira LM, Neto MS, Castilho HD, Garcia EB (2001) Clinical application of the VY posterior thigh fasciocutaneous flap. Rev Assoc Méd Bras 47(4):311–319CrossRefPubMed
2.
Zurück zum Zitat Edsberg LE, Black JM, Goldberg M, McNichol L, Moore L, Sieggreen M (2016) Revised national pressure ulcer advisory panel pressure injury staging system: revised pressure injury staging system. J Wound, Ostomy Continence Nurs 43(6):585CrossRef Edsberg LE, Black JM, Goldberg M, McNichol L, Moore L, Sieggreen M (2016) Revised national pressure ulcer advisory panel pressure injury staging system: revised pressure injury staging system. J Wound, Ostomy Continence Nurs 43(6):585CrossRef
4.
Zurück zum Zitat Robson MC (1997) The role of growth factors in the healing of chronic wounds. Wound Repair Regen 5(1):12–17CrossRefPubMed Robson MC (1997) The role of growth factors in the healing of chronic wounds. Wound Repair Regen 5(1):12–17CrossRefPubMed
5.
Zurück zum Zitat Trengove NJ, Bielefeldt-Ohmann H, Stacey MC (2000) Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8(1):13–25CrossRefPubMed Trengove NJ, Bielefeldt-Ohmann H, Stacey MC (2000) Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8(1):13–25CrossRefPubMed
6.
Zurück zum Zitat de Braekt MM, van Alphen FA, Kuijpers-Jagtman AM, Maltha JC (1991) Effect of low level laser therapy on wound healing after palatal surgery in beagle dogs. Lasers Surg Med 11(5):462–470CrossRef de Braekt MM, van Alphen FA, Kuijpers-Jagtman AM, Maltha JC (1991) Effect of low level laser therapy on wound healing after palatal surgery in beagle dogs. Lasers Surg Med 11(5):462–470CrossRef
7.
Zurück zum Zitat Mester E, Mester AF, Mester A (1985) The biomedical effects of laser application. Lasers Surg Med 5(1):31–39CrossRefPubMed Mester E, Mester AF, Mester A (1985) The biomedical effects of laser application. Lasers Surg Med 5(1):31–39CrossRefPubMed
8.
Zurück zum Zitat Yu W, Naim JO, Lanzafame RJ (1997) Effects of photostimulation on wound healing in diabetic mice. Lasers Surg Med 20(1):56–63CrossRefPubMed Yu W, Naim JO, Lanzafame RJ (1997) Effects of photostimulation on wound healing in diabetic mice. Lasers Surg Med 20(1):56–63CrossRefPubMed
9.
Zurück zum Zitat Maiya GA, Kumar P, Rao L (2005) Effect of low intensity helium-neon (He-Ne) laser irradiation on diabetic wound healing dynamics. Photomed Laser Ther 23(2):187–190CrossRef Maiya GA, Kumar P, Rao L (2005) Effect of low intensity helium-neon (He-Ne) laser irradiation on diabetic wound healing dynamics. Photomed Laser Ther 23(2):187–190CrossRef
10.
Zurück zum Zitat Posten W, Wrone DA, Dover JS, Arndt KA, Silapunt S, Alam M (2005) Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg 31(3):334–340CrossRefPubMed Posten W, Wrone DA, Dover JS, Arndt KA, Silapunt S, Alam M (2005) Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg 31(3):334–340CrossRefPubMed
11.
Zurück zum Zitat Viegas VN, Abreu MER, Viezzer C, Machado DC, Filho MSA, Silva DN, Pagnoncelli RM (2007) Effect of low-level laser therapy on inflammatory reactions during wound healing: comparison with meloxicam. Photomed Laser Surg 25(6):467–473CrossRefPubMed Viegas VN, Abreu MER, Viezzer C, Machado DC, Filho MSA, Silva DN, Pagnoncelli RM (2007) Effect of low-level laser therapy on inflammatory reactions during wound healing: comparison with meloxicam. Photomed Laser Surg 25(6):467–473CrossRefPubMed
12.
Zurück zum Zitat Machado RS, Viana S, and Sbruzzi G (2017) Low-level laser therapy in the treatment of pressure ulcers: systematic review. Lasers Med Sci 32(4):937–944 Machado RS, Viana S, and Sbruzzi G (2017) Low-level laser therapy in the treatment of pressure ulcers: systematic review. Lasers Med Sci 32(4):937–944
13.
Zurück zum Zitat Taradaj J, Halski T, Kucharzewski M, Urbanek T, Halska U, Kucio C (2013) Effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on pressure ulcer healing: results from a clinical study. Evid Based Complement Alternat Med 2013:960240CrossRefPubMedPubMedCentral Taradaj J, Halski T, Kucharzewski M, Urbanek T, Halska U, Kucio C (2013) Effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on pressure ulcer healing: results from a clinical study. Evid Based Complement Alternat Med 2013:960240CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Nussbaum EL, Biemann I, Mustard B (1994) Comparison of ultrasound/ultraviolet-C and laser for treatment of pressure ulcers in patients with spinal cord injury. Phys Ther 74(9):812–823CrossRefPubMed Nussbaum EL, Biemann I, Mustard B (1994) Comparison of ultrasound/ultraviolet-C and laser for treatment of pressure ulcers in patients with spinal cord injury. Phys Ther 74(9):812–823CrossRefPubMed
15.
Zurück zum Zitat Taly AB, Nair KPS, Murali T, John A (2004) Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: a randomized double-blind controlled trial. Arch Phys Med Rehabil 85(10):1657–1661CrossRefPubMed Taly AB, Nair KPS, Murali T, John A (2004) Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: a randomized double-blind controlled trial. Arch Phys Med Rehabil 85(10):1657–1661CrossRefPubMed
16.
Zurück zum Zitat Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 182:72–77CrossRef Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 182:72–77CrossRef
17.
18.
Zurück zum Zitat Saygun I, Nizam N, Ural AU, Serdar MA, Avcu F, Tözüm TF (2012) Low-level laser irradiation affects the release of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3) from osteoblasts. Photomed Laser Surg 30(3):149–154CrossRefPubMed Saygun I, Nizam N, Ural AU, Serdar MA, Avcu F, Tözüm TF (2012) Low-level laser irradiation affects the release of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3) from osteoblasts. Photomed Laser Surg 30(3):149–154CrossRefPubMed
19.
Zurück zum Zitat Dang Y, Liu B, Liu L, Ye X, Bi X, Zhang Y, Gu J (2011) The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating TGF-β/Smad signaling pathway. Lasers Med Sci 26(6):837–843CrossRefPubMed Dang Y, Liu B, Liu L, Ye X, Bi X, Zhang Y, Gu J (2011) The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating TGF-β/Smad signaling pathway. Lasers Med Sci 26(6):837–843CrossRefPubMed
20.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4):402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4):402–408CrossRefPubMed
21.
Zurück zum Zitat Wang CJ, Ko JY, Kuo YR, Yang YJ (2011) Molecular changes in diabetic foot ulcers. Diabetes Res Clin Pract 94(1):105–110CrossRefPubMed Wang CJ, Ko JY, Kuo YR, Yang YJ (2011) Molecular changes in diabetic foot ulcers. Diabetes Res Clin Pract 94(1):105–110CrossRefPubMed
22.
Zurück zum Zitat Rocha J, Miranda M, Andrade M (2006) Pressure ulcer management—evidence-based interventions. Acta Med Port 19(1):29–38 Rocha J, Miranda M, Andrade M (2006) Pressure ulcer management—evidence-based interventions. Acta Med Port 19(1):29–38
23.
Zurück zum Zitat Costa MP, Sturtz G, Costa FPPD, Ferreira MC, Barros Filho TE (2005) Epidemiological profile and treatment of pressure ulcers: experience with 77 cases. Acta Ortop Bras 13(3):124–133CrossRef Costa MP, Sturtz G, Costa FPPD, Ferreira MC, Barros Filho TE (2005) Epidemiological profile and treatment of pressure ulcers: experience with 77 cases. Acta Ortop Bras 13(3):124–133CrossRef
24.
Zurück zum Zitat Lopes LDF (2011) Utilização do laser de 660 nm, 17 J/cm2 em úlceras por pressão− Um relato de caso. Rev Neurocienc 19(4):668–674 Lopes LDF (2011) Utilização do laser de 660 nm, 17 J/cm2 em úlceras por pressão− Um relato de caso. Rev Neurocienc 19(4):668–674
25.
Zurück zum Zitat Santoianni P, Monfrecola G, Martellotta D, Ayala F (1984) Inadequate effect of helium-neon laser on venous leg ulcers. Photo-Dermatology 1(5):245–249PubMed Santoianni P, Monfrecola G, Martellotta D, Ayala F (1984) Inadequate effect of helium-neon laser on venous leg ulcers. Photo-Dermatology 1(5):245–249PubMed
26.
Zurück zum Zitat Malm M, Lundeberg T (1991) Effect of low power gallium arsenide laser on healing of venous ulcers. Scand J Plast Reconstr Surg Hand Surg 25(3):249–251CrossRefPubMed Malm M, Lundeberg T (1991) Effect of low power gallium arsenide laser on healing of venous ulcers. Scand J Plast Reconstr Surg Hand Surg 25(3):249–251CrossRefPubMed
27.
Zurück zum Zitat Lundeberg T, Malm M (1991) Low-power HeNe laser treatment of venous leg ulcers. Ann Plast Surg 27(6):537–539CrossRefPubMed Lundeberg T, Malm M (1991) Low-power HeNe laser treatment of venous leg ulcers. Ann Plast Surg 27(6):537–539CrossRefPubMed
28.
Zurück zum Zitat Gupta AK, Filonenko N, Salansky N, Sauder DN (1998) The use of low energy photon therapy (LEPT) in venous leg ulcers: a double-blind, placebo-controlled study. Dermatol Surg 24(12):1383–1386CrossRefPubMed Gupta AK, Filonenko N, Salansky N, Sauder DN (1998) The use of low energy photon therapy (LEPT) in venous leg ulcers: a double-blind, placebo-controlled study. Dermatol Surg 24(12):1383–1386CrossRefPubMed
29.
Zurück zum Zitat Kirtschig G, Brink A, Scheper R, Jaspars E (2005) Low level laser: does it influence wound healing in venous leg ulcers? A randomized, placebo-controlled, double-blind study. J Clin Microbiol 40:779–787 Kirtschig G, Brink A, Scheper R, Jaspars E (2005) Low level laser: does it influence wound healing in venous leg ulcers? A randomized, placebo-controlled, double-blind study. J Clin Microbiol 40:779–787
30.
Zurück zum Zitat Sobanko JF, Alster TS (2008) Efficacy of low-level laser therapy for chronic cutaneous ulceration in humans: a review and discussion. Dermatol Surg 34(8):991–1000PubMed Sobanko JF, Alster TS (2008) Efficacy of low-level laser therapy for chronic cutaneous ulceration in humans: a review and discussion. Dermatol Surg 34(8):991–1000PubMed
31.
Zurück zum Zitat Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 18(2):72–77CrossRefPubMed Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 18(2):72–77CrossRefPubMed
32.
Zurück zum Zitat Lanzafame RJ, Stadler I, Kurtz AF, Connelly R, Brondon P, Olson D (2007) Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model. Lasers Surg Med 39(6):534–542CrossRefPubMed Lanzafame RJ, Stadler I, Kurtz AF, Connelly R, Brondon P, Olson D (2007) Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model. Lasers Surg Med 39(6):534–542CrossRefPubMed
33.
Zurück zum Zitat Kaviani A, Djavid GE, Ataie-Fashtami L, Fateh M, Ghodsi M, Salami M, Zand N, Kashef N, Larijani B (2011) A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg 29(2):109–114CrossRefPubMed Kaviani A, Djavid GE, Ataie-Fashtami L, Fateh M, Ghodsi M, Salami M, Zand N, Kashef N, Larijani B (2011) A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg 29(2):109–114CrossRefPubMed
34.
Zurück zum Zitat Minatel DG, Frade MAC, França SC, Enwemeka CS (2009) Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med 41(6):433–441CrossRefPubMed Minatel DG, Frade MAC, França SC, Enwemeka CS (2009) Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med 41(6):433–441CrossRefPubMed
35.
Zurück zum Zitat Saied GM, Kamel RM, Labib AM, Said MT, Mohamed AZ (2011) The diabetic foot and leg: combined He-Ne and infrared low-intensity lasers improve skin blood perfusion and prevent potential complications. A prospective study on 30 Egyptian patients. Lasers Med Sci 26(5):627–632CrossRefPubMed Saied GM, Kamel RM, Labib AM, Said MT, Mohamed AZ (2011) The diabetic foot and leg: combined He-Ne and infrared low-intensity lasers improve skin blood perfusion and prevent potential complications. A prospective study on 30 Egyptian patients. Lasers Med Sci 26(5):627–632CrossRefPubMed
36.
Zurück zum Zitat Carvalho PDTCD, Silva ISD, Reis FAD, Perreira DM, Aydos RD (2010) Influence of ingaalp laser (660nm) on the healing of skin wounds in diabetic rats. Acta Cir Bras 25(1):71–79CrossRef Carvalho PDTCD, Silva ISD, Reis FAD, Perreira DM, Aydos RD (2010) Influence of ingaalp laser (660nm) on the healing of skin wounds in diabetic rats. Acta Cir Bras 25(1):71–79CrossRef
37.
Zurück zum Zitat Dixit S, Maiya A, Umakanth S, Borkar S (2013) Photobiomodulation of surgical wound dehiscence in a diabetic individual by low-level laser therapy following median sternotomy. Indian J Palliat Care 19(1):71CrossRefPubMedPubMedCentral Dixit S, Maiya A, Umakanth S, Borkar S (2013) Photobiomodulation of surgical wound dehiscence in a diabetic individual by low-level laser therapy following median sternotomy. Indian J Palliat Care 19(1):71CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Dixit S, Agrawal PR, Sharma DK, Singh RP (2014) Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: case report. Indian J Plast Surg 47(3):432PubMedPubMedCentral Dixit S, Agrawal PR, Sharma DK, Singh RP (2014) Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: case report. Indian J Plast Surg 47(3):432PubMedPubMedCentral
39.
Zurück zum Zitat Kipshidze N, Nikolaychik V, Keelan MH, Shankar LR, Khanna A, Kornowski R et al (2001) Low-power helium: neon laser irradiation enhances production of vascular endothelial growth factor and promotes growth of endothelial cells in vitro. Lasers Surg Med 28(4):355–364CrossRefPubMed Kipshidze N, Nikolaychik V, Keelan MH, Shankar LR, Khanna A, Kornowski R et al (2001) Low-power helium: neon laser irradiation enhances production of vascular endothelial growth factor and promotes growth of endothelial cells in vitro. Lasers Surg Med 28(4):355–364CrossRefPubMed
40.
Zurück zum Zitat Sekhejane PR, Houreld NN, Abrahamse H (2011) Irradiation at 636 nm positively affects diabetic wounded and hypoxic cells in vitro. Photomed Laser Surg 29(8):521–530CrossRefPubMed Sekhejane PR, Houreld NN, Abrahamse H (2011) Irradiation at 636 nm positively affects diabetic wounded and hypoxic cells in vitro. Photomed Laser Surg 29(8):521–530CrossRefPubMed
41.
Zurück zum Zitat Houreld NN, Sekhejane PR, Abrahamse H (2010) Irradiation at 830 nm stimulates nitric oxide production and inhibits pro-inflammatory cytokines in diabetic wounded fibroblast cells. Lasers Surg Med 42(6):494–502CrossRefPubMed Houreld NN, Sekhejane PR, Abrahamse H (2010) Irradiation at 830 nm stimulates nitric oxide production and inhibits pro-inflammatory cytokines in diabetic wounded fibroblast cells. Lasers Surg Med 42(6):494–502CrossRefPubMed
42.
Zurück zum Zitat Pallotta RC, Bjordal JM, Frigo L, Junior ECPL, Teixeira S, Marcos RL et al (2012) Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci 27(1):71–78CrossRefPubMed Pallotta RC, Bjordal JM, Frigo L, Junior ECPL, Teixeira S, Marcos RL et al (2012) Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci 27(1):71–78CrossRefPubMed
43.
Zurück zum Zitat Carvalho MHCD, Colaço AL, Fortes ZB (2006) Cytokines, endothelial dysfunction, and insulin resistance. Arq Bras Endocrinol Metabol 50(2):304–312CrossRefPubMed Carvalho MHCD, Colaço AL, Fortes ZB (2006) Cytokines, endothelial dysfunction, and insulin resistance. Arq Bras Endocrinol Metabol 50(2):304–312CrossRefPubMed
44.
Zurück zum Zitat Tonnesen MG, Feng X, & Clark RA (2000) Angiogenesis in wound healing. In Journal of Investigative Dermatology Symposium Proceedings Vol. 5, No. 1. Nature Publishing Group, pp. 40–46 Tonnesen MG, Feng X, & Clark RA (2000) Angiogenesis in wound healing. In Journal of Investigative Dermatology Symposium Proceedings Vol. 5, No. 1. Nature Publishing Group, pp. 40–46
45.
Zurück zum Zitat Riedel K, Riedel F, Goessler UR, Germann G, Sauerbier M (2007) TGF-β antisense therapy increases angiogenic potential in human keratinocytes in vitro∗. Arch Med Res 38(1):45–51CrossRefPubMed Riedel K, Riedel F, Goessler UR, Germann G, Sauerbier M (2007) TGF-β antisense therapy increases angiogenic potential in human keratinocytes in vitro∗. Arch Med Res 38(1):45–51CrossRefPubMed
Metadaten
Titel
Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers
verfasst von
Anelice Calixto Ruh
Lúcio Frigo
Marcos Fernando Xisto Braga Cavalcanti
Paulo Svidnicki
Viviane Nogaroto Vicari
Rodrigo Alvaro Brandão Lopes-Martins
Ernesto Cesar Pinto Leal Junior
Natalia De Isla
Francesca Diomede
Oriana Trubiani
Giovani Marino Favero
Publikationsdatum
28.11.2017
Verlag
Springer London
Erschienen in
Lasers in Medical Science / Ausgabe 1/2018
Print ISSN: 0268-8921
Elektronische ISSN: 1435-604X
DOI
https://doi.org/10.1007/s10103-017-2384-6

Weitere Artikel der Ausgabe 1/2018

Lasers in Medical Science 1/2018 Zur Ausgabe